Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
Antimicrob Agents Chemother. 1988 Aug; 32(8): 1187–1191.
PMCID: PMC172374

Endogenous active efflux of norfloxacin in susceptible Escherichia coli.


Escherichia coli was shown to have an energy-dependent reduced uptake of the fluoroquinolone antimicrobial agent norfloxacin. Studies of everted inner membrane vesicles suggested that this reduced accumulation involved a carrier-mediated norfloxacin active efflux generated by proton motive force with an apparent Km of 0.2 mM and a Vmax of 3 nmol min-1 mg of protein-1. Other hydrophilic, but not hydrophobic, quinolones competed with norfloxacin for transport. Porin (OmpF)-deficient E. coli cells were twofold less susceptible to norfloxacin and showed twice as much energy-dependent reduction in drug uptake. However, active efflux assayed in everted vesicles from the OmpF strain was unchanged compared with that in the parental strain. These findings suggest that in the OmpF mutant decreased outer membrane permeability, combined with active efflux across the inner membrane, in some manner results in decreased steady-state uptake of norfloxacin and lowered drug susceptibility.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (943K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aoyama H, Sato K, Kato T, Hirai K, Mitsuhashi S. Norfloxacin resistance in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother. 1987 Oct;31(10):1640–1641. [PMC free article] [PubMed]
  • Bedard J, Wong S, Bryan LE. Accumulation of enoxacin by Escherichia coli and Bacillus subtilis. Antimicrob Agents Chemother. 1987 Sep;31(9):1348–1354. [PMC free article] [PubMed]
  • Dano K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta. 1973 Oct 25;323(3):466–483. [PubMed]
  • DAVIS BD, MINGIOLI ES. Mutants of Escherichia coli requiring methionine or vitamin B12. J Bacteriol. 1950 Jul;60(1):17–28. [PMC free article] [PubMed]
  • Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(1):265–269. [PMC free article] [PubMed]
  • George AM, Levy SB. Amplifiable resistance to tetracycline, chloramphenicol, and other antibiotics in Escherichia coli: involvement of a non-plasmid-determined efflux of tetracycline. J Bacteriol. 1983 Aug;155(2):531–540. [PMC free article] [PubMed]
  • Hall MN, Silhavy TJ. The ompB locus and the regulation of the major outer membrane porin proteins of Escherichia coli K12. J Mol Biol. 1981 Feb 15;146(1):23–43. [PubMed]
  • Hirai K, Aoyama H, Irikura T, Iyobe S, Mitsuhashi S. Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob Agents Chemother. 1986 Mar;29(3):535–538. [PMC free article] [PubMed]
  • Hirai K, Aoyama H, Suzue S, Irikura T, Iyobe S, Mitsuhashi S. Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12. Antimicrob Agents Chemother. 1986 Aug;30(2):248–253. [PMC free article] [PubMed]
  • Hooper DC, Wolfson JS. The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother. 1985 Nov;28(5):716–721. [PMC free article] [PubMed]
  • Hooper DC, Wolfson JS, Souza KS, Tung C, McHugh GL, Swartz MN. Genetic and biochemical characterization of norfloxacin resistance in Escherichia coli. Antimicrob Agents Chemother. 1986 Apr;29(4):639–644. [PMC free article] [PubMed]
  • Kessel D, Wilberding C. Anthracycline resistance in P388 murine leukemia and its circumvention by calcium antagonists. Cancer Res. 1985 Apr;45(4):1687–1691. [PubMed]
  • LOWRY OH, ROSEBROUGH NJ, FARR AL, RANDALL RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed]
  • Lundrigan M, Earhart CF. Reduction in three iron-regulated outer membrane proteins and protein a by the Escherichia coli K-12 perA mutation. J Bacteriol. 1981 May;146(2):804–807. [PMC free article] [PubMed]
  • Martin SK, Oduola AM, Milhous WK. Reversal of chloroquine resistance in Plasmodium falciparum by verapamil. Science. 1987 Feb 20;235(4791):899–901. [PubMed]
  • McMurry LM, Aronson DA, Levy SB. Susceptible Escherichia coli cells can actively excrete tetracyclines. Antimicrob Agents Chemother. 1983 Oct;24(4):544–551. [PMC free article] [PubMed]
  • McMurry L, Petrucci RE, Jr, Levy SB. Active efflux of tetracycline encoded by four genetically different tetracycline resistance determinants in Escherichia coli. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3974–3977. [PMC free article] [PubMed]
  • Mobley HL, Rosen BP. Energetics of plasmid-mediated arsenate resistance in Escherichia coli. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6119–6122. [PMC free article] [PubMed]
  • Perlin DS, San Francisco MJ, Slayman CW, Rosen BP. H+/ATP stoichiometry of proton pumps from Neurospora crassa and Escherichia coli. Arch Biochem Biophys. 1986 Jul;248(1):53–61. [PubMed]
  • Silver S, Keach D. Energy-dependent arsenate efflux: the mechanism of plasmid-mediated resistance. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6114–6118. [PMC free article] [PubMed]
  • Winkler HH, Wilson TH. The role of energy coupling in the transport of beta-galactosides by Escherichia coli. J Biol Chem. 1966 May 25;241(10):2200–2211. [PubMed]
  • Wolfson JS, Hooper DC. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother. 1985 Oct;28(4):581–586. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...